Field of the Invention
The present invention relates to the development of bone growth factors as therapeutics for the prevention and treatment of pathological conditions involving bone tissue, for example osteoporosis, Paget's disease, osteopetrosis, fracture repair, periodontal disease and healing of bone defects. The factors of the present invention may also be useful for promoting wound healing and in anti-tumor treatments.
Living bone tissue is continuously being replenished by the process of resorption and deposition of calcium minerals. This process, termed the resorption-formation cycle, is facilitated primarily by two cell types, the osteoblasts and the osteoclasts. The osteoclast is a multinucleated cell (a cell with more than one nucleus) and is the only cell in the body known to have the capacity to degrade (or resorb) bone. This resorption activity is accomplished by the osteoclast forming pits (resorption lacunae) in bone tissue, and, in fact, osteoclast activity in cell culture is measured by their capacity to form these pits on slices of mineralized tissue such as bone or sperm whale dentine. The osteoclast is derived from a hematopoietic precursor which it shares with the formed elements of the blood (Mundy & Roodman (1987) Osteoclast ontogeny and function. In Bone and Mineral Research V: 209-280. (ed. Peck) Elsevier). The precursor for the osteoclast is a mononuclear cell (cell with a single nucleus) which is found in the bone marrow and which forms the mature and unique multinucleated osteoclast after undergoing replication and differentiation by means of cell fusion. The mature osteoclast is distinguished from other multinucleated cells by the presence of the enzyme tartrate-resistant acid phosphatase (TRAP) which is often used as an osteoclast cell marker.
Among the pathological conditions associated with an abnormal osteoclast development or function are conditions wherein increased bone resorption results in the development of fragile and/or brittle bone structure, such as osteoporosis, or increased bone formation results in the development of excess bone mass, such as osteopetrosis. It is believed that the development of excess or deficient populations of osteoclasts or osteoblasts may result from a corresponding lack or excess of specific protein factors called cytokines.